Synthesis and Reactions of Some Heterocycles Containing Nitrogen and Sulphur
Synthesis and Reactions of Some Heterocycles Containing Nitrogen and Sulphur
Synthesis and Reactions of Some Heterocycles Containing Nitrogen and Sulphur
In
Chemistry Science
(Organic)
Department of Chemistry
Faculty of Science, Fayoum
FAYOUM UNIVERSITY
2008
Approval Sheet
/ 2006
Acknowledgments
To Dr. G. H. Tammam,
Assistant Prof. of Organic Chemistry, Chemistry Department, Faculty of
Science, Fayoum University for his support supervision, advice and valuable
criticism.
To Dr. H. M. M. Bakeer,
Assistant Prof. of Organic Chemistry, Chemistry Department, Faculty of
Science, Fayoum University for her continuous guidance, encouragement, kind
assistance and unlimited effort for revising this work.
To Dr. R. M. Abdel-Motelab,
Lecturer of Organic Chemistry, Chemistry Department, Faculty of
Science, Fayoum University for his suggesting and directing the research,
continuous advice and valuable criticism, which made this work possible in its
present form.
SUMMARY
Part I
R`
R
R
CN
R`
CN
CH2COOH
NHCOPh
Ac2O
N
R
C6H5
p-OCH3C6H4
p-CH3C6H4
p-ClC6H4
2-furyl
2-thiophenyl
C6H5
Ph
2a-m
1
Products
2a
2b
2c
2d
2e
2f
2g
R`
H
H
H
H
H
H
CH3
Products
2h
2i
2j
2k
2l
2m
R
R`
p-CH3C6H4
CH3
p-ClC6H4
CH3
2-thiophenyl
CH3
CH3
CH3
Cyclohexyl
CH2CO2Et
CH3
CH3
O
AcOH
ArNH N
N
Ar
N
N
COOEt
CH3
NHCOPh
O
5a, Ar = C6H5
b, Ar = C6H4p-CH3
Ph
3a, Ar = C6H5
b, Ar = C6H4p-CH3
EtOOC
CH3
O
Ph C
H
ArN N Cl
0-5 oC
COOEt
H3C
ROOC
EtOOC
RONa / ROH
N
H
Ph
PhCHO/TEA
Ph
4
CH3
EtOOC
O
ArNH2
Ph
NH2NH2
12a, Ar = C6H5
b, Ar = C6H4p-C
PhNHNH2
EtOH/
CH3 O
CH3 O
NH
NH
N Ar
Ph
EtOH/r.t.
EtOOC
CH3
2m
8, R = CH3
10, R = CH2CH3
EtOOC
N
N
Ph
Ph
14a
14b
Scheme 1
H
Ph
Part II
Reactions of 4-Substituted Oxazolones with ,-Unsaturated Nitriles:
A Novel Synthesis of 1,2,4-Triazol-3-yl Pyrans, Oxazol-4-yl Pyrans
and Their Annulated Derivatives
2-Phenyl-4-phenylhydrazono-4H-oxazol-5-one 1 reacts with 2-(propan2-ylidene)-malono-nitrile, 2-(1-thiophen-2-yl-ethylidene)-malononitrile, 2cyclohexylidene-malononitrile, 2-cyclopentylid-ene-malononitrile, 2-(1-(2oxo-2H-chromen-3-yl)-ethylidene)malononitrile, 3-cyano-4-methyl coumarin,
5-cyano-4-methyl-6-oxo-1-phenyl-1,6-dihydro-pyridazine-3-carboxylic
acid
ethyl ester or 2-aminoprop-1-ene-1,1,3-tricarbo-nitrile in sodium/ dry dioxane
to yield 1,2,4-triazol-3-yl-pyran derivatives 3-11 respectively (Scheme 1).
O
O
Ph
N N
Ph
CN
Ph
CN
N N
Ph
N N
Ph
Ph
6
S
4
5
iii
CN
viii
ii
O
Ph
CN
N N
Ph-NH-N
v
N
Ph
CH3
3
O
O
NC
NC
vii =
H2N
vi
Ph
N N
Ph
N
N
CN
NC
CN
CN
ii =
CH3
iii =
iv =
O
CN
viii =
CH2CN
CH3
CN
CH3
N N
Ph
CN
11
Ph
CN
NC
CN
CH3 vi =
v=
NC
S
Ph
NH2
CONH2
COOEt
i=
H3C
Ph
CN
vii
NC
N N
Ph
Ph
Ph
iv
N N
Ph
Scheme 1
O
NC
H3C
N
N
Ph
COOEt
O
Ar
Ar/
O
Ph
13a, Ar = C6H5, Ar/ = C6H5
b, Ar = C6H5, Ar/ = C6H4-Cl-p
c, Ar = C6H4-Cl-p, Ar/ = C6H5
d, Ar = C6H4-NO2-p, Ar/ = C6H5
e, Ar = C6H4-OCH3-p, Ar/ = C6H5
f, Ar = C6H5, Ar/ = thiophen-2-yl
i
NH O
NH O
`
O
iii
Ph
O
ArCH
N
N
Ph
Ph
Ph
15
N
N
ii
COOEt
N
Ph
16
2
iv
NH
CN
O
Ph
O
N
Ph
O
NC
i=
Ar`
CN
NC
ii =
CH3 H3C
N
N
O
14
CN
Ph
COOEt
CN
NC
CH3
iii =
CH3
iv =
O
Scheme 2
Ph
Part III
Synthesis and Reactions of Some New 2-Phenyl-4-(Substituted
Thiophen-2-yl-hydrazono)-4H-Oxazol-5-ones
Diazotization
of
2-amino-4,5,6,7-tetrahydro-benzo[b]thiophene-3carboxylic acid ethyl ester, 2-amino-5,6-dihydro-4H-cyclopenta-[b]thiophene3-carboxylic acid ethyl ester or 2-amino-4-aryl-thiophene-3-carbonitrile with
sodium nitrite/HCl yielding the diazonium salts which on treating with hippuric
acid/acetic anhydride mixture in the presence of sodium acetate trihydrate
affording the 2-phenyl-4-(substituted thiophen-2-yl-hydrazono)-4H-oxazol-5ones 1a-d.
Y
Z
X
S
Y
Z
NH2
X
S
NaNO2 / HCl
0 oC / AcOH
Y
Z
X
S
N NCl
hippuric acid
Ac2O /AcONa
O
O
NH-N
N
Ph
1a, X = CO2Et, Y-Z = -(CH2)4b, X = CO2Et, Y-Z = -(CH2)3c, X = CN, Y = C6H5, Z = H
d, X = CN, Y = C6H4-OCH3p, Z = H
CO2Et
S
CO2Et
N
N
Ph
NHCH2COOH
Ph
C Ph
H
CO2Et
S
Ph
iv
vi
O
CO2Et
S
Ph
N
Ph
CO2Et
N
1a
CO2Et
vii
Ph
Ph
iii
CN
O
C
Y
CH
X
H
N
10
CONHNH2
O
N
N
C
ii
S
Ph
2a, X = COOEt, Y = CN
b, X = Y = CN
c, -X-Y- = -CONHCNC
Y
i = H2C ii = NH2NH2 iii =
X
Ph
NH2
vii =
NH2
NH2
N
HO
NH
CN
iv = glycine v = PhCHO,Ac2O, AcONa vi =
CH3
COOH
NH2
Scheme 1
CO2Et
S
N
Ph
N
CONHAr
N
11a, Ar = C6H5
b, Ar = C6H4-CH3p
Ar-NH2
1a
CO2Et
RNHNH2
EtOH / TEA
12a, R = H
b, R = Ph
CO2Et
N
Ph
CONHNHR
N
Ph
N
COOEt
PhCHO
15
CO2Et
S
N
Ph
13
Scheme 2
N
CONHN
N
CHPh
Part IV
Synthesis and Some Reactions of 4-(2-alkyl-2-arylhydrazono)-2Phenyloxazol-5-one Derivatives
A series of new 4-(2-alkyl-2-arylhy-drazono)-2-phenyloxazol-5-ones
derivatives 2a-d were synthesized by reaction of the oxazolones 1a, b with
methyl or ethyl iodides. On the other hand trial to alkylate 1a with methyl
bromoacetate or phenacyl bromide afforded the triazine 6 and pyridinone 10
respectively (Scheme 1).
The reaction of 2a, b with ammonia, primary aromatic amines or
hydrazines gave the acyclic amides 14a, b, 17a-d and hydrazides 20a-d
respectively. Cyclization of 14a, b and 17a, b gave imidazoles 16a, b, and
19a, b respectively. While cyclization of 20a-d afforded triazines 21a, b and
24a, b. Boiling compounds 21a, b in acetic acid containing concentrated HCl
affording the triazinone derivatives 23a, b (Scheme 2).
R
Ar N N
Ph
2 a, Ar = C6H5, R = CH3
b, Ar = C6H4-pCH3, R = CH3
c, Ar = C6H5, R = CH3-CH2
d, Ar = C6H4-pCH3, R =CH3-CH2
Ph
H3CO2C
N
Ph
6
-CO2
R-X / K2CO3
H
Ar N N
CH2CO2CH3
O
CH2CO2CH3 Ph N N
Ph N COOH
N
N O Br
N O
N
K2CO3
H3CO2C
Ph
Ph
Ph
1 a, Ar = C6H5
4
8
b, Ar = C6H4-pCH3
O
2 PhCOCH2Br / K2CO3
O
PhNHN
Br
N
Br
Ph
O
COPh - 2HBr
PhNHN
COPh
N
COPh
COPh
Ph
10
11
Scheme 1
2a, b
CH3COONH4
or HCONH2
CH3
CH3
Ar N N
CH3
Ar N N
CONH2
CH3COOH
NH
NH-COPh
CH3COOH
R=Ph
CONHAr`
20 a, Ar = C6H5, R= H
17a, Ar = C6H5, Ar` = C6H5
b, Ar = C6H5, R = C6H5
b, Ar = C6H5, Ar` = C6H4-CH3-o
c, Ar = C6H4-CH3-p, R = H
c, Ar = C6H5, Ar` = 2-pyridyl
d, Ar = C6H4-CH3-p, R = C6H5
d, Ar = C6H5 Ar` = 2-thiazolyl
14 a, Ar = C6H5
b, Ar = C6H4-CH3-P
CH3
Ar N N
CONHNHR
NH-COPh
NH-COPh
Ar N N
Ar`NH2
R-NHNH2
N
N
H
Ar-N-N
Ar-N-N
CH3COOH
R=H
CH3
N
N
Ph
Ar N N
COCH3
Ph
Ph
O
N Ar`
Ph
Ph
21a, Ar = C6H5
24 a, Ar = C6H5
16 a, Ar = C6H5
19a, Ar = C6H5, Ar` = C6H5
b, Ar = C6H4-CH3-P b, Ar = C6H4-CH3-P b, Ar = C6H5, Ar` = C6H4-CH3-o
b, Ar = C6H4-CH3-P
AcOH/HCl
O
Ar-N=N
N
NH
N
Ph
23 a, Ar = C6H5
b, Ar = C6H4-CH3-P
Scheme 2